The purpose of this conference is to discuss and refine alternatives study designs: alternative methodologies to randomized controlled trials (RCTs). The proposed conference dates will be April 7-8, 2005. The revised conference will focus discussions on alternative study designs to determine comparative effectiveness of treatments for clinical decision-making: (1) analyses of existing administrative databases such as Medicare and HCUP databases, MDS data from long-term care settings, data from registries, etc.; (2) quasi-experimental designs such as systematic treatments designs, before-after or interrupted time series designs, longitudinal designs, and cross-sectional designs; and (3) Clinical Practice Improvements study designs. Our ultimate goal is to expand the potential infrastructure for conducting clinical research within the health care delivery system by increasing knowledge about rigorous alternative designs among researchers and policymakers. The goal of this conference is to identify, describe, or refine a variety of rigorous research methodologies that incorporate natural variation within data from routine clinical practice to determine what works, for whom, when, and at what cost. We will invite health services researchers, behavior researchers, and study design experts, high-level stakeholders (clinicians and other providers, institutions, health plans, journal editors, foundations), and policy makers in Federal, State, and local governments, and voluntary associations to engage in a critical examination of ways to improve the design of studies, data collection, and use of information about comparative effectiveness of treatments. We will produce a study guide that summarizes the conference deliberations: Alternative Study Design Guide for Evidence-based Practice: Harnessing Natural Variation for Effectiveness Research. This guide will help disseminate conference ideas and products beyond the participants attending the conference.